Interleukin-2 (IL-2) has been extensively studied in clinical trials and its antitumor activity has been more limited than initially anticipated. Nevertheless, the durable complete response observed in a subset of patients with extensive metastatic disease warrants further investigation of IL-2. One of the major obstacles with IL-2 based therapy has been the substantial acute toxicity observed in patients receiving high dose IL-2 (HDIL-2). We have been developing new low-dose IL-2 (LDIL-2) and determining their preclinical efficacy. One of our approaches to decrease IL-2-induced toxicity and simultaneously increase its antitumor activity is to combine LDIL-2 with bryostatin-1. Bryostatin-1, has direct antitumor and immunomodulatory effects. Furthermore, it is synergistic with IL-2 in activating the immune system and this is important because patient with cancer and also elderly individuals have an impaired immune response. The biological basis of this impaired function is poorly understood. However, it has been reported that both antigen presenting cells and T cells are dysfunctional in tumor bearing host suggesting that defective antigen presentation and altered T cell responses in cancer patients may account for the lack of an efficient antitumor response. Our data suggest the following: 1) IL-2 and bryostatin-1 inhibits tumor growth in vivo; 2) the combination of bryostatin-1 and LD-IL-2 enhances the ability of monocytes and DC to act as efficient APCs; and 3) Bryostatin-1 and IL-2 induces a Th1 type of cytokine response. We hypothesize that some of the immune alterations observed in cancer patients could be reversed by bryostatin-1 and LDIL-2. Therefore, as a necessary step toward the development of immune strategies and to test our hypothesis we are conducting a phase I clinical trial in patients with cancer that is addressing the following specific aims: I- Determine the safety and toxicity associated with the administration of bryostatin-1 and LDIL-2; II- Determine the effects of bryostatin-1 and LDIL-2 on the functional and molecular status of APC and T cells; III- Record any antitumor response that occurs in response to the regimen.